Differential effects of two calcium channel blockers on bronchial smooth muscle

The effects of the new Ca(2+)-entry blocker SK&F 96365 (1-¿beta-[4-methoxyphenyl)propoxy]-4-methoxy-phenethyl¿-1H- imidazole hydrochloride, [sequence: see text] CAS 130495-35-1) and nifedipine on the contractile response of guinea-pig trachea to KCl and histamine are described. Diameter changes of cannulated, perfused tubes of guinea-pig trachea were recorded by a computerized video-microscopy bioassay system. In order to determine whether the capacitive calcium entry is the major mechanism in the guinea-pig trachea, the effects of SK&F 96365, an antagonist of the second-messenger operated channel, were studied. The results of experiments in Ca(2+)-free medium containing EGTA (0.1 mmol l-1) indicate that KCl- and histamine evoked contractions are mainly due to an influx of extracellular Ca2+ rather than due to release from intracellular stores. SK&F 96365 (10 mumol l-1) showed a more effective antispasmogenic activity on histamine-induced contraction of guinea-pig trachea than the voltage-operated channel (VOC)-blocker nifedipine (10 mumol l-1). Nifedipine is only effective in inhibiting KCl induced contraction. These results may have significance for the use of agents such as SK&F 96365 in the treatment of asthma.